NCT00219557

AG-013736 In Combination With Gemcitabine Versus Gemcitabine Alone For Patients With Metastatic Pancreatic Cancer

Completed Phase 2 Results posted Last updated 14 May 2019

What this trial tests

Phase 2 trial testing Gemcitabine in Pancreatic Neoplasms in 111 participants. Completed in 14 March 2008.

Timeline

5 July 2005

Primary endpoint
14 March 2008

14 March 2008

Quick facts

Lead sponsor	Pfizer
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	111
Start date	5 July 2005
Primary completion	14 March 2008
Estimated completion	14 March 2008
Sites	38 locations across France, Italy, Belgium, United Kingdom, Germany, Canada, United States, Spain

Drugs / interventions tested

• Gemcitabine (gemcitabine) — full drug profile →
• AG-013736 — full drug profile →
• Gemcitabine (gemcitabine) — full drug profile →

Conditions studied

• Pancreatic Neoplasms — all drugs for Pancreatic Neoplasms →

Sponsor

Pfizer — full company profile →

Who can join

18 and older, any sex, with Pancreatic Neoplasms. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Overall Survival (OS) Primary · Baseline of Phase 2 to death or until at least 1 year after the randomization of the last participant

Time in days from randomization to date of death due to any cause. OS was calculated as the death date minus the date of randomization plus 1. Death was determined from adverse event data (where outcome was death) or from follow-up contact data (where the participant current status was death).

Group	Value	95% CI
Axitinib + Gemcitabine	210	162 – 308
Gemcitabine	171	125 – 267

Dose Confirmation of Axitinib (AG-013736) on Basis of Number of Participants With Dose Limiting Toxicity (DLT) Secondary · Phase 1 baseline up to Week 4

Dose of axitinib (AG-013736) was confirmed if not more than 1 out of 6 participants experienced a DLT during first cycle. DLT included grade (Gr) 4 neutropenia or thrombocytopenia, greater than or equal to (\>=) Gr 3 anemia or non hematological toxicities for \>= 7 days (except alopecia) or \>= Gr 1 hemoptysis or \>=2 gram /24 hours proteinuria or inability to resume background chemotherapy or axitinib (AG-013736) dosing within 14 days of stopping due to treatment related toxicity.

Group	Value	95% CI
Axitinib + Gemcitabine (Phase 1 Lead-In)	0

Dose Confirmation of Gemcitabine on Basis of Number of Participants With Dose Limiting Toxicity (DLT) Secondary · Phase 1 Baseline up to Week 4

Dose of gemcitabine was confirmed if not more than 1 out of 6 participants experienced a DLT during first cycle. DLT included grade (Gr) 4 neutropenia or thrombocytopenia, greater than or equal to (\>=) Gr 3 anemia or non hematological toxicities for \>= 7 days (except alopecia) or \>= Gr 1 hemoptysis or \>=2 gram /24 hours proteinuria or inability to resume background chemotherapy or axitinib (AG-013736) dosing within 14 days of stopping due to treatment related toxicity.

Group	Value	95% CI
Axitinib + Gemcitabine (Phase 1 Lead-In)	0

Maximum Observed Plasma Concentration (Cmax) for Axitinib (AG-013736) Secondary · 0 (pre-dose), 0.5, 1, 1.5, 2, 3.5, 4.5, 9.5, and 12.5 hours (hr) post-dose on Day 15 of Phase 1 Cycle 1

Group	Value	95% CI
Axitinib + Gemcitabine (Phase 1 Lead-In)	45.08	± 34.32

Area Under the Curve From Time Zero to 24 Hours [AUC (0-24)] of Axitinib (AG-013736) Secondary · 0 (pre-dose), 0.5, 1, 1.5, 2, 3.5, 4.5, 9.5, and 12.5 hr post-dose on Day 15 of Phase 1 Cycle 1

AUC (0-24) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to 24 hours (0-24).

Group	Value	95% CI
Axitinib + Gemcitabine (Phase 1 Lead-In)	282.34	± 135.27

Time to Reach Maximum Observed Plasma Concentration (Tmax) of Axitinib (AG-013736) Secondary · 0 (pre-dose), 0.5, 1, 1.5, 2, 3.5, 4.5, 9.5, and 12.5 hr post-dose on Day 15 of Phase 1 Cycle 1

Tmax was based on the actual time points when the samples were collected.

Group	Value	95% CI
Axitinib + Gemcitabine (Phase 1 Lead-In)	1.52	0.50 – 2.20

Plasma Decay Half-life (t1/2) of Axitinib (AG-013736) Secondary · 0 (pre-dose), 0.5, 1, 1.5, 2, 3.5, 4.5, 9.5, and 12.5 hr post-dose on Day 15 of Phase 1 Cycle 1

Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

Group	Value	95% CI
Axitinib + Gemcitabine (Phase 1 Lead-In)	2.97	± 1.95

Maximum Observed Plasma Concentration (Cmax) of Gemcitabine Secondary · 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 9 and 12 hr after start of infusion on Day 15 of Phase 1 Cycle 1

Group	Value	95% CI
Axitinib + Gemcitabine (Phase 1 Lead-In)	27280.0	± 12599.1

Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of Gemcitabine Secondary · 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 9 and 12 hr after start of infusion on Day 15 of Phase 1 Cycle 1

AUC (0 - ∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞).

Group	Value	95% CI
Axitinib + Gemcitabine (Phase 1 Lead-In)	13656.00	± 4142.16

Plasma Decay Half-life (t1/2) of Gemcitabine Secondary · 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 9 and 12 hr after start of infusion on Day 15 of Phase 1 Cycle 1

Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

Group	Value	95% CI
Axitinib + Gemcitabine (Phase 1 Lead-In)	0.310	± 0.028

Percentage of Participants With Overall Response (OR) Secondary · Phase 2 baseline to disease progression or discontinuation from study, assessed every 8 weeks up to 80 weeks

Percentage of participants with OR based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. CR are defined as the disappearance of all lesions (target and/or non-target). PR are those with at least 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum of longest dimensions.

Group	Value	95% CI
Axitinib + Gemcitabine	7.2	2.4 – 16.1
Gemcitabine	2.9	0.1 – 15.3

Duration of Response (DR) Secondary · Phase 2 baseline to disease progression or discontinuation from study due to any cause, assessed every 8 weeks up to 80 weeks

Time in days from the first documentation of objective tumor response to objective tumor progression or death due to any cancer. Duration of tumor response was calculated as the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR that was subsequently confirmed plus 1. DR was calculated for the subgroup of participants with a confirmed objective tumor response.

Group	Value	95% CI
Axitinib + Gemcitabine	379	136 – 379
Gemcitabine	155	NA – NA

Adverse events — posted to ClinicalTrials.gov

Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Axitinib + Gemcitabine (Phase 1 Lead-In)

Serious: 3/8 (38%)

Deaths: —

Axitinib + Gemcitabine

Serious: 35/68 (51%)

Deaths: —

Gemcitabine

Serious: 10/31 (32%)

Deaths: —

Serious adverse events (81 terms)

Reaction	System	Axitinib + Gemcitabine (Ph…	Axitinib + Gemcitabine	Gemcitabine
Disease progression	General disorders	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—
Asthenia	General disorders	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—
Dehydration	Metabolism and nutrition disorders	—	—	—
Pyrexia	General disorders	—	—	—
Atrial fibrillation	Cardiac disorders	—	—	—
Abdominal strangulated hernia	Gastrointestinal disorders	—	—	—
Intestinal obstruction	Gastrointestinal disorders	—	—	—
Nausea	Gastrointestinal disorders	—	—	—
Pneumonia	Infections and infestations	—	—	—
Sepsis	Infections and infestations	—	—	—
Failure to thrive	Metabolism and nutrition disorders	—	—	—
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	—	—	—
Deep vein thrombosis	Vascular disorders	—	—	—
Disseminated intravascular coagulation	Blood and lymphatic system disorders	—	—	—
Thrombocytopenia	Blood and lymphatic system disorders	—	—	—
Atrial flutter	Cardiac disorders	—	—	—
Myocardial infarction	Cardiac disorders	—	—	—
Pericardial effusion	Cardiac disorders	—	—	—
Tachycardia	Cardiac disorders	—	—	—
Abdominal distension	Gastrointestinal disorders	—	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—	—

Other adverse events (276 terms — click to expand)

Reaction	System	Axitinib + Gemcitabine (Ph…	Axitinib + Gemcitabine	Gemcitabine
Diarrhoea	Gastrointestinal disorders	—	—	—
Nausea	Gastrointestinal disorders	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—
Fatigue	General disorders	—	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—	—
Asthenia	General disorders	—	—	—
Constipation	Gastrointestinal disorders	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—
Weight decreased	Investigations	—	—	—
Hypertension	Vascular disorders	—	—	—
Neutropenia	Blood and lymphatic system disorders	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—
Stomatitis	Gastrointestinal disorders	—	—	—
Mucosal inflammation	General disorders	—	—	—
Pyrexia	General disorders	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—
Rash	Skin and subcutaneous tissue disorders	—	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—	—
Oedema peripheral	General disorders	—	—	—
Hypokalaemia	Metabolism and nutrition disorders	—	—	—
Thrombocytopenia	Blood and lymphatic system disorders	—	—	—
Pain	General disorders	—	—	—
Alopecia	Skin and subcutaneous tissue disorders	—	—	—
Dyspepsia	Gastrointestinal disorders	—	—	—
Urinary tract infection	Infections and infestations	—	—	—
Headache	Nervous system disorders	—	—	—
Anxiety	Psychiatric disorders	—	—	—
Dizziness	Nervous system disorders	—	—	—
Epistaxis	Respiratory, thoracic and mediastinal disorders	—	—	—
Dysgeusia	Nervous system disorders	—	—	—
Depression	Psychiatric disorders	—	—	—
Oral pain	Gastrointestinal disorders	—	—	—
Oedema	General disorders	—	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—	—
Lethargy	Nervous system disorders	—	—	—
Insomnia	Psychiatric disorders	—	—	—
Proteinuria	Renal and urinary disorders	—	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—	—
Ascites	Gastrointestinal disorders	—	—	—

Most-reported serious reactions: Disease progression, Dyspnoea, Abdominal pain, Anaemia, Asthenia, Diarrhoea, Dehydration, Pyrexia.

Data from ClinicalTrials.gov NCT00219557 adverse events section.

Sponsor's own description

This is a Phase 2 study being conducted at multiple centers in the United States, Europe and Canada. Patients having pancreatic cancer that is locally advanced or that has spread to other parts of the body (i.e., metastatic) are eligible to participate. Patients must have not had any prior systemic treatment for advanced disease. The purpose of the study is to test whether the angiogenesis inhibitor Axitinib \[AG-013736\] in combination with gemcitabine is an effective treatment for advanced pancreatic cancer vs. gemcitabine alone by overall survival.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Angiogenic signaling pathways and anti-angiogenic therapy for cancer.
   Liu ZL, Chen HH, Zheng LL, Sun LP, et al · · 2023 · cited 808× · PMID 37169756 · DOI 10.1038/s41392-023-01460-1
2. Efficacy of gemcitabine plus axitinib compared with gemcitabine alone in patients with advanced pancreatic cancer: an open-label randomised phase II study.
   Spano JP, Chodkiewicz C, Maurel J, Wong R, et al · · 2008 · cited 184× · PMID 18514303 · DOI 10.1016/s0140-6736(08)60661-3
3. Cancer combination therapies by angiogenesis inhibitors; a comprehensive review.
   Ansari MJ, Bokov D, Markov A, Jalil AT, et al · · 2022 · cited 117× · PMID 35392964 · DOI 10.1186/s12964-022-00838-y
4. Advanced pancreatic adenocarcinoma: a review of current treatment strategies and developing therapies.
   Teague A, Lim KH, Wang-Gillam A. · · 2015 · cited 103× · PMID 25755680 · DOI 10.1177/1758834014564775
5. Antiangiogenic therapy in human gastrointestinal malignancies.
   Heidemann J, Binion DG, Domschke W, Kucharzik T. · · 2006 · cited 5× · PMID 16966704 · DOI 10.1136/gut.2005.088229
6. Recent Advances and Challenges in the Treatment of Advanced Pancreatic Cancer: An Update on Completed and Ongoing Clinical Trials.
   Shenoy A, Yousif A, Hussain MD. · · 2025 · cited 3× · PMID 40282495 · DOI 10.3390/cancers17081319
7. Unraveling the interplay: exploring signaling pathways in pancreatic cancer in the context of pancreatic embryogenesis.
   Swain S, Narayan RK, Mishra PR. · · 2024 · cited 1× · PMID 39239563 · DOI 10.3389/fcell.2024.1461278
8. Comparison of simple models of periodic protocols for combined anticancer therapy.
   Dołbniak M, Swierniak A. · · 2013 · PMID 23653666 · DOI 10.1155/2013/567213